The effects of Celecoxib on inflammation and synovial microcirculation in murine antigen-induced arthritis.

摘要

OBJECTIVE: There is controversy about the effects of cyclooxygenase-2 (COX-2) on adhesion molecules and the microvasculature in inflamed tissue. Thus, the aim of this study was to assess COX-2-expression in Antigen-induced Arthritis (AiA) and to investigate the effects of selective COX-2 inhibition by Celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide) (CXB), on synovial microcirculation and adhesion molecule expression in arthritic as well as healthy mice. METHODS: Balb/c mice were allocated to 4 groups; 2 control groups with saline or CXB and 2 groups with AiA which also received saline or CXB (30 mg/kg BW in 0.3 ml solution). The severity of arthritis was assessed by changes in the transverse joint diameter On day 14 after AiA-induction, the patella tendon of the left knee joint was microsurgically resected and intravital fluorescence microscopy on synovial tissue was performed. Finally, the knee joint was removed for histology and immunohistochmistry. RESULTS: COX-2-expression in the inflamed synovium was demonstrated by immunohistochemistry. Application of Celecoxib resulted in a significant reduction in the rolling leukocyte fraction as well as in the number of leukocytes adherent to the endothelium (0.25 +/- 0. 1 and 96 +/- 34 cells/mm2 respectively) in comparison to the untreated animals with AiA (0.44 +/- 0.03 and 206 +/- 22 cells/mm2 respectively). Additionally, CXB-treated arthritic animals showed significantly less knee joint swelling and reduced adhesion molecule expression. CONCLUSION: In the present study, COX-2 expression in the synovial tissue of mice with AiA could be demonstrated. Selective COX-2 inhibition with CXB resulted in reduced leucocyte-endothelial cell interactions and decreased adhesion molecule expression. Evidence for a protective role of COX-2 in mouse AiA was not found.